OBJECTIVES: To identify the carcinogenic substances in betel nut and in unburned chewing tobacco. APPROACH: Standard chemical procedures will be utilized to separate the active agents from these substances. The relative carcinogenic activity of the various fractions will be assessed by their ability to produce epithelial tumors after topical applications to the mucosa of the hamster buccal pouch. Carcinogenicity of the fractions will also be assessed by their ability to produce tumors after injection into grafts of fetal oral tissue implanted into isologous hamster buccal pouch mucosa.